Abstract
The goal of this study was to investigate the function of phosphatidylethanolamine-binding protein 4 (PEBP4) in invasion and metastasis of non-small cell lung cancer (NSCLC). PEBP4 mRNA and protein expression in 56 cases of NSCLC tissues were detected using RT-PCR and Western blot, and the relationship between PEBP4 expression and invasion and metastasis of NSCLC was analyzed. The change in the invasive ability of human NSCLC cell line HCC827 was observed after knocking down PEBP4 expression using RNA interference. PEBP4 mRNA and protein expression in cancer tissues of patients with lymph node metastasis were significantly higher than those in patients without lymph node metastasis (p < 0.05). PEBP4 expression significantly decreased in HCC827 cells after transfection with PEBP4 siRNA (p < 0.01), and the number of HCC827 cells that migrated through Transwell chambers was significantly lower than that of non-transfected control and transfected control cells (p < 0.01). PEBP4 over-expression may promote the invasion and metastasis of NSCLC.
Similar content being viewed by others
References
Al-Mulla F, Bitar MS, Al-Maghrebi M, Behbehani AI, Al-Ali W, Rath O, Doyle B, Tan KY, Pitt A, Kolch W. Raf kinase inhibitor protein RKIP enhances signaling by glycogen synthase kinase-3beta. Cancer Res. 2011;71(4):1334–43.
Shao WL, Wang DY, He JX. The role of gene expression profiling in early-stage non-small cell lung cancer. J Thorac Dis. 2010;2(2):89–99.
Bernier I, Jolles P. Purification and characterization of a basic 23 kDa cytosolic protein from bovine brain. Biochim Biophys Acta. 1984;790(2):174–81.
Garcia R, Grindlay J, Rath O, Fee F, Kolch W. Regulation of human myoblast differentiation by PEBP4. EMBO Rep. 2009;10(3):278–84.
Amaya I, Ratcliffe OJ, Bradley DJ. Expression of CENTRORADIALIS (CEN) and CEN-like genes in tobacco reveals a conserved mechanism controlling phase change in diverse species. Plant Cell. 1999;11(8):1405–18.
Erttmann KD, Gallin MY. Onchocerca volvulus: identification of cDNAs encoding a putative phosphatidyl-ethanolamine-binding protein and a putative partially processed mRNA precursor. Gene. 1996;174(2):203–7.
Gu X, Ma C, Yuan D, Song Y. Circulating soluble intercellular adhesion molecule-1 in lung cancer: a systematic review. Transl Lung Cancer Res. 2011. doi:10.3978/j.issn.2218-6751.08.01.
Kikuchi R, Kawahigashi H, Ando T, Tonooka T, Handa H. Molecular and functional characterization of PEBP genes in barley reveal the diversification of their roles in flowering. Plant Physiol. 2009;149(3):1341–53.
Odabaei G, Chatterjee D, Jazirehi AR, Goodglick L, Yeung K, Bonavida B. Raf-1 kinase inhibitor protein: structure, function, regulation of cell signaling, and pivotal role in apoptosis. Adv Cancer Res. 2004;91:169–200.
Yeung K, Seitz T, Li S, Janosch P, McFerran B, Kaiser C, Fee F, Katsanakis KD, Rose DW, Mischak H, Sedivy JM, Kolch W. Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP. Nature. 1999;401(6749):173–7.
Corbit KC, Trakul N, Eves EM, Diaz B, Marshall M, Rosner MR. Activation of Raf-1 signaling by protein kinase C through a mechanism involving Raf kinase inhibitory protein. J Biol Chem. 2003;278(15):13061–8.
Shemon AN, Heil GL, Granovsky AE, Clark MM, McElheny D, Chimon A, Rosner MR, Koide S. Characterization of the Raf kinase inhibitory protein (RKIP) binding pocket: NMR-based screening identifies small-molecule ligands. PLoS One. 2010;5(5):e10479.
Zaravinos A, Chatziioannou M, Lambrou GI, Boulalas I, Delakas D, Spandidos DA. Implication of RAF and RKIP genes in urinary bladder cancer. Pathol Oncol Res. 2011;17(2):181–90.
Wang X, Li N, Liu B, Sun H, Chen T, Li H, Qiu J, Zhang L, Wan T, Cao X. A novel human phosphatidylethanolamine-binding protein resists tumor necrosis factor alpha-induced apoptosis by inhibiting mitogen-activated protein kinase pathway activation and phosphatidylethanolamine externalization. J Biol Chem. 2004;279(44):45855–64.
Qiu J, Xiao J, Han C, Li N, Shen X, Jiang H, Cao X. Potentiation of tumor necrosis factor-alpha-induced tumor cell apoptosis by a small molecule inhibitor for anti-apoptotic protein hPEBP4. J Biol Chem. 2010;285(16):12241–7.
Liu H, Qiu J, Li N, Chen T, Cao X. Human phosphatidylethanolamine-binding protein 4 promotes transactivation of estrogen receptor alpha (ERalpha) in human cancer cells by inhibiting proteasome-dependent ERalpha degradation via association with Src. J Biol Chem. 2010;285(29):21934–42.
Xiao DK, He JX. Epithelial mesenchymal transition and lung cancer. J Thorac Dis. 2010;2(3):154–9.
Zhang Y, Wang X, Xiang Z, Li H, Qiu J, Sun Q, Wan T, Li N, Cao X, Wang J. Promotion of cellular migration and apoptosis resistance by a mouse eye-specific phosphatidylethanolamine-binding protein. Int J Mol Med. 2007;19(1):55–63.
Wang X, Li N, Li H, Liu B, Qiu J, Chen T, Cao X. Silencing of human phosphatidylethanolamine-binding protein 4 sensitizes breast cancer cells to tumor necrosis factor-alpha-induced apoptosis and cell growth arrest. Clin Cancer Res. 2005;11(20):7545–53.
Yeung K, Janosch P, McFerran B, Rose DW, Mischak H, Sedivy JM, Kolch W. Mechanism of suppression of the Raf/MEK/extracellular signal-regulated kinase pathway by the raf kinase inhibitor protein. Mol Cell Biol. 2000;20(9):3079–85.
Li H, Wang X, Li N, Qiu J, Zhang Y, Cao X. hPEBP4 resists TRAIL-induced apoptosis of human prostate cancer cells by activating Akt and deactivating ERK1/2 pathways. J Biol Chem. 2007;282(7):4943–50.
Winn RA, Marek L, Han SY, Rodriguez K, Rodriguez N, Hammond M, Van Scoyk M, Acosta H, Mirus J, Barry N, Bren-Mattison Y, Van Raay TJ, Nemenoff RA, Heasley LE. Restoration of Wnt-7a expression reverses non-small cell lung cancer cellular transformation through frizzled-9-mediated growth inhibition and promotion of cell differentiation. J Biol Chem. 2005;280(20):19625–34.
Niquet J, Wasterlain CG. Bim, Bad, and Bax: a deadly combination in epileptic seizures. J Clin Invest. 2004;113(7):960–2.
Jeong SJ, Pise-Masison CA, Radonovich MF, Park HU, Brady JN. Activated AKT regulates NF-kappaB activation, p53 inhibition and cell survival in HTLV-1-transformed cells. Oncogene. 2005;24(44):6719–28.
Ahmed NN, Grimes HL, Bellacosa A, Chan TO, Tsichlis PN. Transduction of interleukin-2 antiapoptotic and proliferative signals via Akt protein kinase. Proc Natl Acad Sci U S A. 1997;94(8):3627–32.
Lee MY, Ryu JM, Lee SH, Park JH, Han HJ. Lipid rafts play an important role for maintenance of embryonic stem cell self-renewal. J Lipid Res. 2010;51(8):2082–9.
Li P, Wang X, Li N, Kong H, Guo Z, Liu S, Cao X. Anti-apoptotic hPEBP4 silencing promotes TRAIL-induced apoptosis of human ovarian cancer cells by activating ERK and JNK pathways. Int J Mol Med. 2006;18(3):505–10.
Qian Y, Corum L, Meng Q, Blenis J, Zheng JZ, Shi X, Flynn DC, Jiang BH. PI3K induced actin filament remodeling through Akt and p70S6K1: implication of essential role in cell migration. Am J Physiol Cell Physiol. 2004;286(1):C153–63.
Syed DN, Afaq F, Sarfaraz S, Khan N, Kedlaya R, Setaluri V, Mukhtar H. Delphinidin inhibits cell proliferation and invasion via modulation of Met receptor phosphorylation. Toxicol Appl Pharmacol. 2008;231(1):52–60.
Kim D, Kim S, Koh H, Yoon SO, Chung AS, Cho KS, Chung J. Akt/PKB promotes cancer cell invasion via increased motility and metalloproteinase production. FASEB J. 2001;15(11):1953–62.
Yu HG, Li JY, Yang YN, Luo HS, Yu JP, Meier JJ, Schrader H, Bastian A, Schmidt WE, Schmitz F. Increased abundance of cyclooxygenase-2 correlates with vascular endothelial growth factor-A abundance and tumor angiogenesis in gastric cancer. Cancer Lett. 2003;195(1):43–51.
Tahanian E, Sanchez LA, Shiao TC, Roy R, Annabi B. Flavonoids targeting of IkappaB phosphorylation abrogates carcinogen-induced MMP-9 and COX-2 expression in human brain endothelial cells. Drug Des Devel Ther. 2011;5:299–309.
Maroni P, Matteucci E, Luzzati A, Perrucchini G, Bendinelli P, Desiderio MA. Nuclear co-localization and functional interaction of COX-2 and HIF-1alpha characterize bone metastasis of human breast carcinoma. Breast Cancer Res Treat. 2011;129(2):433–50.
Tammali R, Saxena A, Srivastava SK, Ramana KV. Aldose reductase inhibition prevents hypoxia-induced increase in hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) by regulating 26 S proteasome-mediated protein degradation in human colon cancer cells. J Biol Chem. 2011;286(27):24089–100.
Yang HH, Zhang Q, He JX, Lu WJ. Regulation of calcium signaling in lung cancer. J Thorac Dis. 2010;2(1):52–6.
Zuo JH, Zhu W, Li MY, Li XH, Yi H, Zeng GQ, Wan XX, He QY, Li JH, Qu JQ, Chen Y, Xiao ZQ. Activation of EGFR promotes squamous carcinoma SCC10A cell migration and invasion via inducing EMT-like phenotype change and MMP-9-mediated degradation of E-cadherin. J Cell Biochem. 2011;112(9):2508–17.
Conflicts of interest
None
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yu, GP., Huang, B., Chen, GQ. et al. PEBP4 gene expression and its significance in invasion and metastasis of non-small cell lung cancer. Tumor Biol. 33, 223–228 (2012). https://doi.org/10.1007/s13277-011-0265-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-011-0265-3